Identification

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Name
Oseltamivir
Accession Number
DB00198  (APRD01148)
Type
Small Molecule
Groups
Approved
Description

Oseltamivir (also known as the marketed product TamifluⓇ), is an antiviral neuraminidase inhibitor used for the treatment and prophylaxis of infection with influenza viruses A (including pandemic H1N1) and B. Oseltamivir exerts its antiviral activity by inhibiting the activity of the viral neuraminidase enzyme found on the surface of the virus, which prevents budding from the host cell, viral replication, and infectivity.

The clinical benefit of use of oseltamivir is greatest when administered within 48 hours of the onset of influenza symptoms since effectiveness decreases significantly after that point in time; there is generally no benefit in use beyond 48 hours for healthy, low-risk individuals as influenza is a self-limiting illness.10,19,11 However, antiviral treatment might be beneficial when initiated after 48 hours for patients with severe, complicated or progressive illness or for hospitalized patients.12 According to the CDC, data from clinical trials and observational studies have demonstrated that early antiviral treatment can shorten the duration of fever and illness symptoms, and may reduce the risk of some complications (including pneumonia and respiratory failure). They recommend the use of oseltamivir in people with a higher risk of developing complications including children younger than 2 years, people over 65 years, people with some chronic conditions or immunosuppression, pregnant women, residents of long term care facilities, and indigenous communities for example.18

The benefits of oseltamivir use are controversial; a 2014 Cochrane Review of the evidence found that oseltamivir treatment had limited benefit. The authors concluded that oseltamivir use in healthy adults had small, non-specific effects on symptoms (where the time to first alleviation of symptoms was only reduced from 7 to 6.3 days), it had no effect on hospitalizations, and that there was no evidence for any reductions in complications of influenza such as pneumonia.7,8,9 Due to the risk of adverse effects such as nausea, vomiting, psychiatric effects and renal adverse events in adults and vomiting in children, the harms are generally considered to outweigh the small clinical benefit of use of oseltamivir.

Notably, in 2017, the World Health Organization downgraded oseltamivir from its essential medicines list from a "core" drug to a "complementary" drug, due to limited cost-effectiveness.6 Yearly vaccination with the influenza vaccine is still considered the best preventative measure.

Structure
Thumb
Synonyms
  • (−)-oseltamivir
  • 1-Cyclohexene-1-carboxylic acid, 4-(acetylamino)-5-amino-3-(1-ethylpropoxy)-, ethyl ester, (3R-(3alpha,4beta,5alpha))-
  • Ethyl (3R,4R,5S)-4-acetamido-5-amino-3-(1-ethylpropoxy)-1-cyclohexene-1-carboxylate
  • Oseltamivir
  • Oséltamivir
  • Oseltamivirum
External IDs
GS 4104 / GS-4071 ETHYL ESTER / GS-4104 / GS4104 / HSDB 7433 / RO-64-0796 / RO-640796 / RO64-0796
Product Ingredients
IngredientUNIICASInChI Key
Oseltamivir phosphate4A3O49NGEZ204255-11-8PGZUMBJQJWIWGJ-ONAKXNSWSA-N
Active Moieties
NameKindUNIICASInChI Key
Oseltamivir acidunknownK6106LV5Q8187227-45-8NENPYTRHICXVCS-YNEHKIRRSA-N
Product Images
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
TamifluCapsule75 mg/1OralA-S Medication Solutions1999-10-27Not applicableUs50090 066220180907 15195 eo8wbz
TamifluCapsule75 mg/1OralPhysicians Total Care, Inc.2002-10-28Not applicableUs00004 0800 85 nlmimage10 491e24c1
TamifluPowder, for suspension6 mg/1mLOralGenentech, Inc.2011-03-21Not applicableUs
TamifluCapsule30 mgOralRoche Registration Gmb H2002-06-20Not applicableEu
TamifluPowder, for suspension6 mg/1mLOralGenentech, Inc.2011-07-112011-03-21Us
TamifluCapsule75 mg/1OralA-S Medication Solutions1999-10-27Not applicableUs54569 488820180907 15195 pu3zzg
TamifluCapsule45 mg/1OralPhysicians Total Care, Inc.2009-10-30Not applicableUs00004 0801 85 nlmimage10 8e41c70e
TamifluPowder, for suspension6 mgOralHoffmann La Roche2012-09-10Not applicableCanada
TamifluCapsule75 mg/1OralGenentech, Inc.1999-10-27Not applicableUs0004 080020180810 16125 mil71e
TamifluPowder, for suspension12 mg/mlOralRoche Registration Gmb H2002-06-20Not applicableEu
Additional Data Available
  • Application Number
    Application Number

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

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  • Product Code
    Product Code

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

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Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
EbilfuminCapsule45 mgOralActavis Group Ptc Ehf.2014-05-22Not applicableEu
EbilfuminCapsule30 mgOralActavis Group Ptc Ehf.2014-05-22Not applicableEu
EbilfuminCapsule75 mgOralActavis Group Ptc Ehf.2014-05-22Not applicableEu
EbilfuminCapsule30 mgOralActavis Group Ptc Ehf.2014-05-22Not applicableEu
EbilfuminCapsule75 mgOralActavis Group Ptc Ehf.2014-05-22Not applicableEu
EbilfuminCapsule45 mgOralActavis Group Ptc Ehf.2014-05-22Not applicableEu
Mylan-oseltamivirCapsuleOralMylan PharmaceuticalsNot applicableNot applicableCanada
Mylan-oseltamivirCapsuleOralMylan PharmaceuticalsNot applicableNot applicableCanada
Mylan-oseltamivirCapsuleOralMylan PharmaceuticalsNot applicableNot applicableCanada
Nat-oseltamivirCapsuleOralNatco Pharma Limited2018-02-06Not applicableCanada
Additional Data Available
  • Application Number
    Application Number

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

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  • Product Code
    Product Code

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

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International/Other Brands
Tamiflu
Categories
UNII
20O93L6F9H
CAS number
196618-13-0
Weight
Average: 312.4045
Monoisotopic: 312.204907394
Chemical Formula
C16H28N2O4
InChI Key
VSZGPKBBMSAYNT-RRFJBIMHSA-N
InChI
InChI=1S/C16H28N2O4/c1-5-12(6-2)22-14-9-11(16(20)21-7-3)8-13(17)15(14)18-10(4)19/h9,12-15H,5-8,17H2,1-4H3,(H,18,19)/t13-,14+,15+/m0/s1
IUPAC Name
ethyl (3R,4R,5S)-5-amino-4-acetamido-3-(pentan-3-yloxy)cyclohex-1-ene-1-carboxylate
SMILES
CCOC(=O)C1=C[C@@H](OC(CC)CC)[C@H](NC(C)=O)[C@@H](N)C1

Pharmacology

Indication

According to FDA prescribing information, oseltamivir is indicated for the treatment of acute, uncomplicated illness due to influenza A and B infection in patients 2 weeks of age and older who have been symptomatic for no more than 48 hours 20. In particular, this agent is indicated in adults and children including full-term neonates who present with symptoms typical of influenza when influenza virus is circulating in the community. Efficacy has been demonstrated when treatment is initiated within two days of the first onset of symptoms.21

Oseltamivir is also indicated for the prophylaxis of influenza in patients one year and older 20. Specifically, post-exposure prevention in individuals one year of age or older following contact with a clinically diagnosed influenza case when influenza virus is circulating in the community qualifies for such prophylactic therapy. Oseltamivir would only be indicated for post-exposure prevention of influenza in infants less than 1 year of age during a pandemic influenza outbreak. 21

Associated Conditions
Pharmacodynamics

There have been postmarketing reports of delirium and abnormal behavior leading to injury, and in some cases resulting in fatal outcomes, in patients with influenza who were receiving oseltamivir. Because these events were reported voluntarily during clinical practice, estimates of frequency cannot be made but they appear to be uncommon based on oseltamivir. These events were reported primarily among pediatric patients and often had an abrupt onset and rapid resolution. The contribution of oseltamivir to these events has not been established. Influenza can be associated with a variety of neurologic and behavioral symptoms that can include events such as hallucinations, delirium, and abnormal behavior, in some cases resulting in fatal outcomes. These events may occur in the setting of encephalitis or encephalopathy but can occur without obvious severe disease.21,13,14

Mechanism of action

Oseltamivir phosphate is a pro-drug of the active metabolite (oseltamivir carboxylate) which is a potent and selective inhibitor of influenza virus neuraminidase enzymes, which are glycoproteins found on the virion surface. Viral neuraminidase enzyme activity is important for viral entry into uninfected cells, for the release of recently formed virus particles from infected cells, and for the further spread of the infectious virus in the body.21,15,22 Oseltamivir activity reduces viral shedding and infectivity.

Oseltamivir is effective agaisnt viral neuraminidases of influenza A (including pandemic H1N1) and influenza B.21,15,22

TargetActionsOrganism
ANeuraminidase
inhibitor
Influenza A virus (strain A/Chile/1/1983 H1N1)
USialidase-1
inhibitor
Humans
USialidase-2
inhibitor
Humans
Additional Data Available
Adverse Effects

Comprehensive structured data on known drug adverse effects with statistical prevalence. MedDRA and ICD10 ids are provided for adverse effect conditions and symptoms.

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Additional Data Available
Contraindications

Structured data covering drug contraindications. Each contraindication describes a scenario in which the drug is not to be used. Includes restrictions on co-administration, contraindicated populations, and more.

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Additional Data Available
Blackbox Warnings

Structured data representing warnings from the black box section of drug labels. These warnings cover important and dangerous risks, contraindications, or adverse effects.

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Absorption

Oseltamivir is readily absorbed from the gastrointestinal tract after oral administration of oseltamivir phosphate and is extensively converted by predominantly hepatic esterases to the active metabolite oseltamivir carboxylate. At least 75 % of an oral dose reaches the systemic circulation as the active metabolite. Exposure to the pro-drug is less than 5 % relative to the active metabolite. Plasma concentrations of both pro-drug and active metabolite are proportional to dose and are unaffected by co-administration with food.20,21,15,22 Pharmacokinetic parameters following twice daily dosing of oseltamivir 75mg capsules are as follows: Cmax of oseltamivir and oseltamivir carboxylate were found to be 65ng/mL and 348ng/mL, respectively, while AUC (0-12h) of oseltamivir and oseltamivir carboxylate were found to be 112ng·h/mL and 2719ng·h/mL, respectively.21

Volume of distribution

The mean volume of distribution at steady state of the oseltamivir carboxylate ranges approximately between 23 and 26 liters in humans, a volume that is roughly equivalent to extracellular body fluid. Since neuraminidase activity is extracellular, oseltamivir carboxylate distributes to all sites of influenza virus spread.20,21,15,22

Protein binding

The binding of the active oseltamivir carboxylate metabolite to human plasma protein is negligible at approximately 3 % while the binding of oseltamivir to human plasma protein is 42%, which is insufficient to cause significant displacement-based drug interactions.20

Metabolism

Oseltamivir is extensively converted to the active metabolite, oseltamivir carboxylate, by esterases located predominantly in the liver. Oseltamivir carboxylate is not further metabolized. Neither oseltamivir nor oseltamivir carboxylate is a substrate for, or inhibitor of, cytochrome P450 isoforms. No phase 2 conjugates of either compound have been identified in vivo.20,21,15,22

Route of elimination

Following absorption, oseltamivir is more than 90 % eliminated through conversion to oseltamivir carboxylate and subsequent elimination entirely through renal excretion. During clinical studies, less than 20 % of oral radiolabelled dose was found to be eliminated in faeces.20,21,15,22

Half life

Plasma concentrations of oseltamivir declined with a half-life of 1 to 3 hours in most subjects after oral administration, although plasma concentrations of oseltamivir carboxylate declined with a half-life of 6 to 10 hours in most subjects after oral administration.20,21

Clearance

Renal clearance (18.8 l/h) of the drug exceeds glomerular filtration rate (7.5 l/h) indicating that tubular secretion occurs in addition to glomerular filtration.21

Toxicity

Reports of overdoses with oseltamivir have been received from clinical trials and during postmarketing experience. In the majority of cases reporting overdose, no adverse reactions were reported. Adverse reactions reported following overdose were similar in nature to those observed with therapeutic doses of oseltamivir.

Affected organisms
  • Influenza A virus
  • Influenza B virus
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
AbacavirOseltamivir may decrease the excretion rate of Abacavir which could result in a higher serum level.
AcarboseOseltamivir may decrease the excretion rate of Acarbose which could result in a higher serum level.
AceclofenacAceclofenac may decrease the excretion rate of Oseltamivir which could result in a higher serum level.
AcemetacinAcemetacin may decrease the excretion rate of Oseltamivir which could result in a higher serum level.
AcetaminophenOseltamivir may decrease the excretion rate of Acetaminophen which could result in a higher serum level.
AcetazolamideAcetazolamide may increase the excretion rate of Oseltamivir which could result in a lower serum level and potentially a reduction in efficacy.
Acetylsalicylic acidAcetylsalicylic acid may decrease the excretion rate of Oseltamivir which could result in a higher serum level.
AclidiniumOseltamivir may decrease the excretion rate of Aclidinium which could result in a higher serum level.
AcrivastineOseltamivir may decrease the excretion rate of Acrivastine which could result in a higher serum level.
AcyclovirAcyclovir may decrease the excretion rate of Oseltamivir which could result in a higher serum level.
Additional Data Available
  • Extended Description
    Extended Description

    Extended description of the mechanism of action and particular properties of each drug interaction.

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  • Severity
    Severity

    A severity rating for each drug interaction, from minor to major.

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  • Evidence Level
    Evidence Level

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  • Action
    Action

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Food Interactions
  • Take without regard to meals. Food may improve gastric tolerance.

References

Synthesis Reference
US5763483
General References
  1. Chokephaibulkit K, Uiprasertkul M, Puthavathana P, Chearskul P, Auewarakul P, Dowell SF, Vanprapar N: A child with avian influenza A (H5N1) infection. Pediatr Infect Dis J. 2005 Feb;24(2):162-6. [PubMed:15702046]
  2. de Jong MD, Tran TT, Truong HK, Vo MH, Smith GJ, Nguyen VC, Bach VC, Phan TQ, Do QH, Guan Y, Peiris JS, Tran TH, Farrar J: Oseltamivir resistance during treatment of influenza A (H5N1) infection. N Engl J Med. 2005 Dec 22;353(25):2667-72. [PubMed:16371632]
  3. Kiso M, Mitamura K, Sakai-Tagawa Y, Shiraishi K, Kawakami C, Kimura K, Hayden FG, Sugaya N, Kawaoka Y: Resistant influenza A viruses in children treated with oseltamivir: descriptive study. Lancet. 2004 Aug 28-Sep 3;364(9436):759-65. [PubMed:15337401]
  4. Ward P, Small I, Smith J, Suter P, Dutkowski R: Oseltamivir (Tamiflu) and its potential for use in the event of an influenza pandemic. J Antimicrob Chemother. 2005 Feb;55 Suppl 1:i5-i21. [PubMed:15709056]
  5. Cooper NJ, Sutton AJ, Abrams KR, Wailoo A, Turner D, Nicholson KG: Effectiveness of neuraminidase inhibitors in treatment and prevention of influenza A and B: systematic review and meta-analyses of randomised controlled trials. BMJ. 2003 Jun 7;326(7401):1235. doi: 10.1136/bmj.326.7401.1235. [PubMed:12791735]
  6. Kmietowicz Z: WHO downgrades oseltamivir on drugs list after reviewing evidence. BMJ. 2017 Jun 12;357:j2841. doi: 10.1136/bmj.j2841. [PubMed:28607038]
  7. Jefferson T, Jones MA, Doshi P, Del Mar CB, Hama R, Thompson MJ, Spencer EA, Onakpoya I, Mahtani KR, Nunan D, Howick J, Heneghan CJ: Neuraminidase inhibitors for preventing and treating influenza in healthy adults and children. Cochrane Database Syst Rev. 2014 Apr 10;(4):CD008965. doi: 10.1002/14651858.CD008965.pub4. [PubMed:24718923]
  8. Michiels B, Van Puyenbroeck K, Verhoeven V, Vermeire E, Coenen S: The value of neuraminidase inhibitors for the prevention and treatment of seasonal influenza: a systematic review of systematic reviews. PLoS One. 2013;8(4):e60348. doi: 10.1371/journal.pone.0060348. Epub 2013 Apr 2. [PubMed:23565231]
  9. Ebell MH, Call M, Shinholser J: Effectiveness of oseltamivir in adults: a meta-analysis of published and unpublished clinical trials. Fam Pract. 2013 Apr;30(2):125-33. doi: 10.1093/fampra/cms059. Epub 2012 Sep 20. [PubMed:22997224]
  10. McQuade B, Blair M: Influenza treatment with oseltamivir outside of labeled recommendations. Am J Health Syst Pharm. 2015 Jan 15;72(2):112-6. doi: 10.2146/ajhp140390. [PubMed:25550133]
  11. Hsu J, Santesso N, Mustafa R, Brozek J, Chen YL, Hopkins JP, Cheung A, Hovhannisyan G, Ivanova L, Flottorp SA, Saeterdal I, Wong AD, Tian J, Uyeki TM, Akl EA, Alonso-Coello P, Smaill F, Schunemann HJ: Antivirals for treatment of influenza: a systematic review and meta-analysis of observational studies. Ann Intern Med. 2012 Apr 3;156(7):512-24. doi: 10.7326/0003-4819-156-7-201204030-00411. Epub 2012 Feb 27. [PubMed:22371849]
  12. Louie JK, Yang S, Acosta M, Yen C, Samuel MC, Schechter R, Guevara H, Uyeki TM: Treatment with neuraminidase inhibitors for critically ill patients with influenza A (H1N1)pdm09. Clin Infect Dis. 2012 Nov;55(9):1198-204. doi: 10.1093/cid/cis636. Epub 2012 Jul 26. [PubMed:22843781]
  13. Toovey S, Prinssen EP, Rayner CR, Thakrar BT, Dutkowski R, Koerner A, Chu T, Sirzen-Zelenskaya A, Britschgi M, Bansod S, Donner B: Post-marketing assessment of neuropsychiatric adverse events in influenza patients treated with oseltamivir: an updated review. Adv Ther. 2012 Oct;29(10):826-48. doi: 10.1007/s12325-012-0050-8. Epub 2012 Oct 2. [PubMed:23054689]
  14. Toovey S, Rayner C, Prinssen E, Chu T, Donner B, Thakrar B, Dutkowski R, Hoffmann G, Breidenbach A, Lindemann L, Carey E, Boak L, Gieschke R, Sacks S, Solsky J, Small I, Reddy D: Assessment of neuropsychiatric adverse events in influenza patients treated with oseltamivir: a comprehensive review. Drug Saf. 2008;31(12):1097-114. doi: 10.2165/0002018-200831120-00006.. [PubMed:19026027]
  15. Electronic Medicines Compendium: Tamiflu (oseltamivir phosphate) 30 mg Hard Capsules Monograph [Link]
  16. Lupin launches US Tamiflu generic amid worst flu season in recent memory: Press Release [Link]
  17. Dailymed - Oseltamivir (FDA) [Link]
  18. CDC Influenza Antiviral Medications: Summary for Clinicians [Link]
  19. Canadian Paediatric Society - The use of antiviral drugs for influenza: Guidance for practitioners [Link]
  20. Oseltamivir FDA Label [File]
  21. Oseltamivir EMA Label [File]
  22. Oseltamivir New Zealand Product Information [File]
External Links
Human Metabolome Database
HMDB0014343
KEGG Drug
D00900
KEGG Compound
C08092
PubChem Compound
65028
PubChem Substance
46507602
ChemSpider
58540
BindingDB
5025
ChEBI
7798
ChEMBL
CHEMBL1229
Therapeutic Targets Database
DAP000714
PharmGKB
PA450721
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Oseltamivir
ATC Codes
J05AH02 — Oseltamivir
AHFS Codes
  • 08:18.28 — Neuraminidase Inhibitors

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedNot AvailableHealthy Volunteers4
1CompletedBasic ScienceDrug Drug Interaction (DDI)1
1CompletedBasic ScienceHealthy Volunteers1
1CompletedHealth Services ResearchAvian Influenza A Virus1
1CompletedOtherInfluenza, Human1
1CompletedTreatmentEnd Stage Renal Disease (ESRD)1
1CompletedTreatmentFlu caused by Influenza3
1CompletedTreatmentFlu caused by Influenza / Virus Diseases1
1CompletedTreatmentHealthy Volunteers5
1CompletedTreatmentHealthy Volunteers / Influenza A, Influenza B1
1CompletedTreatmentInfluenza in Humans1
1TerminatedTreatmentFlu caused by Influenza1
1WithdrawnBasic ScienceFlu caused by Influenza / Pregnancy1
1WithdrawnTreatmentHealthy Volunteers1
1, 2CompletedNot AvailableBMI >30 kg/m21
1, 2CompletedTreatmentFlu caused by Influenza3
1, 2RecruitingTreatmentFlu caused by Influenza1
2CompletedOtherHealthy Volunteers1
2CompletedPreventionFlu caused by Influenza1
2CompletedTreatmentCritical Illness / Flu caused by Influenza / Influenza, Human1
2CompletedTreatmentFlu caused by Influenza4
2CompletedTreatmentFlu caused by Influenza / Influenza, Avian / Severe Influenza1
2CompletedTreatmentFocus of Study / Thrombocytopenias1
2CompletedTreatmentInfluenza A Virus1
2CompletedTreatmentInfluenza A Virus Infection1
2CompletedTreatmentVirus Diseases1
2Not Yet RecruitingTreatmentEpidemic Influenza1
2Not Yet RecruitingTreatmentFlu caused by Influenza1
2RecruitingTreatmentFlu caused by Influenza1
2RecruitingTreatmentInfluenza A Virus Infection3
2TerminatedTreatmentInfluenza A Infection1
2TerminatedTreatmentInfluenza A Virus1
2TerminatedTreatmentVirus Diseases1
2WithdrawnTreatmentFlu caused by Influenza1
2WithdrawnTreatmentInfluenza - Type A Strains1
2, 3WithdrawnTreatmentFlu caused by Influenza1
3CompletedTreatmentFlu caused by Influenza6
3CompletedTreatmentFlu caused by Influenza / Influenza, Human1
3CompletedTreatmentFlu caused by Influenza / Lower Respiratory Tract Infection (LRTI) / Pneumonia / Upper Respiratory Tract Infections / Viral Shedding1
3CompletedTreatmentInfluenza, Human2
3Not Yet RecruitingTreatmentFlu caused by Influenza1
3RecruitingTreatmentFlu caused by Influenza2
3RecruitingTreatmentImmune Thrombocytopenia1
3RecruitingTreatmentInfluenza, Human1
3TerminatedTreatmentFlu caused by Influenza / Upper Respiratory Tract Infections1
3TerminatedTreatmentGastric Influenza1
4Active Not RecruitingTreatmentFlu caused by Influenza1
4CompletedNot AvailableDrug Therapy, Combination1
4CompletedNot AvailableFlu caused by Influenza1
4CompletedBasic ScienceFlu caused by Influenza1
4CompletedBasic ScienceMetabolic Diseases1
4CompletedPreventionFlu caused by Influenza4
4CompletedTreatmentFlu caused by Influenza4
4CompletedTreatmentFlu caused by Influenza / Pneumonia1
4CompletedTreatmentFlu caused by Influenza / Respiratory Tract Infections (RTI)1
4Not Yet RecruitingTreatmentFlu caused by Influenza3
4RecruitingTreatmentFlu caused by Influenza1
4TerminatedNot AvailableFlu caused by Influenza1
4TerminatedHealth Services ResearchFlu caused by Influenza1
4TerminatedTreatmentFlu caused by Influenza2
4TerminatedTreatmentFlu caused by Influenza / Influenza, Human1
4Unknown StatusPreventionFlu caused by Influenza1
4Unknown StatusTreatmentFlu caused by Influenza1
4WithdrawnPreventionFlu caused by Influenza / Pulmonary Diseases1
Not AvailableActive Not RecruitingPreventionInfluenza, Human1
Not AvailableCompletedNot AvailableFlu caused by Influenza1
Not AvailableCompletedNot AvailablePrematurity of Fetus1
Not AvailableCompletedTreatmentFlu caused by Influenza1
Not AvailableCompletedTreatmentInfluenza A Virus Infection1
Not AvailableCompletedTreatmentInfluenza, Human1
Not AvailableRecruitingTreatmentFlu caused by Influenza1
Not AvailableRecruitingTreatmentSevere Influenza1
Not AvailableWithdrawnBasic ScienceInfluenza A Virus Infection / Influenza B Virus Infection1

Pharmacoeconomics

Manufacturers
  • Hoffmann la roche inc
Packagers
  • A-S Medication Solutions LLC
  • Diversified Healthcare Services Inc.
  • DSM Corp.
  • F Hoffmann La Roche Ltd.
  • F Hoffmann-La Roche Ltd.
  • Nucare Pharmaceuticals Inc.
  • Physicians Total Care Inc.
  • Redpharm Drug
Dosage forms
FormRouteStrength
CapsuleOral30 mg
CapsuleOral45 mg
CapsuleOral75 mg
CapsuleOral30 mg/1
For suspensionOral6 mg/1mL
CapsuleOral45 mg/1
CapsuleOral75 mg/1
Powder, for suspensionOral12 mg/1mL
Powder, for suspensionOral12 mg/ml
Powder, for suspensionOral6 mg
Powder, for suspensionOral6 mg/1mL
Powder, for suspensionOral6 mg/ml
CapsuleOral
Powder, for suspensionOral
Prices
Unit descriptionCostUnit
Tamiflu 10 30 mg capsule Box101.54USD box
Tamiflu 10 45 mg capsule Box101.54USD box
Tamiflu 10 75 mg capsule Disp Pack101.54USD disp
Tamiflu 12 mg/ml Suspension51.0USD bottle
Tamiflu 30 mg gel capsule9.76USD gel capsule
Tamiflu 45 mg gel capsule9.76USD gel capsule
Tamiflu 75 mg gel capsule9.76USD gel capsule
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
CA2188835No2006-08-082016-02-26Canada
US5763483Yes1998-06-092017-02-23Us
US5866601Yes1999-02-022016-08-02Us
US5952375Yes1999-09-142015-08-27Us
Additional Data Available
  • Filed On
    Filed On

    The date on which a patent was filed with the relevant government.

    Learn more

Properties

State
Solid
Experimental Properties
PropertyValueSource
water solubilitySolubleNot Available
logP1Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.686 mg/mLALOGPS
logP1.3ALOGPS
logP1.16ChemAxon
logS-2.7ALOGPS
pKa (Strongest Acidic)14.03ChemAxon
pKa (Strongest Basic)9.31ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area90.65 Å2ChemAxon
Rotatable Bond Count8ChemAxon
Refractivity84.2 m3·mol-1ChemAxon
Polarizability34.65 Å3ChemAxon
Number of Rings1ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9156
Blood Brain Barrier-0.9535
Caco-2 permeable-0.702
P-glycoprotein substrateSubstrate0.5919
P-glycoprotein inhibitor INon-inhibitor0.5415
P-glycoprotein inhibitor IINon-inhibitor0.9771
Renal organic cation transporterNon-inhibitor0.9429
CYP450 2C9 substrateNon-substrate0.9083
CYP450 2D6 substrateNon-substrate0.8276
CYP450 3A4 substrateSubstrate0.5283
CYP450 1A2 substrateNon-inhibitor0.8367
CYP450 2C9 inhibitorNon-inhibitor0.8774
CYP450 2D6 inhibitorNon-inhibitor0.9174
CYP450 2C19 inhibitorNon-inhibitor0.6677
CYP450 3A4 inhibitorNon-inhibitor0.8364
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.8682
Ames testNon AMES toxic0.6907
CarcinogenicityNon-carcinogens0.8863
BiodegradationNot ready biodegradable0.6191
Rat acute toxicity2.2695 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9826
hERG inhibition (predictor II)Non-inhibitor0.9464
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-01t9-0193000000-f5d60d35ef59bb0d3d88
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-014i-0930000000-4bafe71e1cfce532c69e
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-014i-0900000000-b47b81a2da926f1b38a0
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-01bi-0900000000-e54a66b05b36ac125c76
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-00dr-0900000000-a088a5ae7a49e423f645
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-004i-0090000000-a4689c9d2708c9864683
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-07fr-0393000000-c4ca6313b8a95857501f
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-014i-0920000000-274bd00e87c126ea0431
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-014i-1900000000-ab2b530339386266bb5e
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-00y3-3900000000-503de5f1484e1733b933
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-006x-6900000000-c732121f239f135b134c
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-006x-9600000000-414288f436e77a96401f
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-07fr-0393000000-782bc585f56c5193cc4e
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-014i-0920000000-2a6c0c1f08190d6bbc0f
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-014i-1900000000-3ea178c0a288c37e3e79
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-00y3-3900000000-0c790adae380f41f557a
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-006x-6900000000-793d9a5e1ce9de381e4f
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-006x-9600000000-ebf8dd7bcfb3a4844078
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-004i-0090000000-f5e9b54d2909b3aff88d
LC-MS/MS Spectrum - LC-APPI-QQ , positiveLC-MS/MSsplash10-0690-0890000000-01c66fcaa8da4e75ec27
LC-MS/MS Spectrum - LC-APPI-QQ , positiveLC-MS/MSsplash10-03fr-0198000000-2773c5bc7f4f4826038e

Taxonomy

Description
This compound belongs to the class of organic compounds known as gamma amino acids and derivatives. These are amino acids having a (-NH2) group attached to the gamma carbon atom.
Kingdom
Organic compounds
Super Class
Organic acids and derivatives
Class
Carboxylic acids and derivatives
Sub Class
Amino acids, peptides, and analogues
Direct Parent
Gamma amino acids and derivatives
Alternative Parents
Enoate esters / Acetamides / Secondary carboxylic acid amides / Monocarboxylic acids and derivatives / Dialkyl ethers / Organopnictogen compounds / Organic oxides / Monoalkylamines / Hydrocarbon derivatives / Carbonyl compounds
Substituents
Gamma amino acid or derivatives / Enoate ester / Acetamide / Alpha,beta-unsaturated carboxylic ester / Carboxamide group / Carboxylic acid ester / Secondary carboxylic acid amide / Dialkyl ether / Ether / Monocarboxylic acid or derivatives
Molecular Framework
Aliphatic homomonocyclic compounds
External Descriptors
diester, primary amino compound, acetamides, amino acid ester, cyclohexenecarboxylate ester (CHEBI:7798)

Targets

Kind
Protein
Organism
Influenza A virus (strain A/Chile/1/1983 H1N1)
Pharmacological action
Yes
Actions
Inhibitor
General Function
Metal ion binding
Specific Function
Catalyzes the removal of terminal sialic acid residues from viral and cellular glycoconjugates. Cleaves off the terminal sialic acids on the glycosylated HA during virus budding to facilitate virus...
Gene Name
NA
Uniprot ID
P11485
Uniprot Name
Neuraminidase
Molecular Weight
51874.045 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423]
  3. McKimm-Breschkin J, Trivedi T, Hampson A, Hay A, Klimov A, Tashiro M, Hayden F, Zambon M: Neuraminidase sequence analysis and susceptibilities of influenza virus clinical isolates to zanamivir and oseltamivir. Antimicrob Agents Chemother. 2003 Jul;47(7):2264-72. [PubMed:12821478]
  4. Du QS, Wang SQ, Chou KC: Analogue inhibitors by modifying oseltamivir based on the crystal neuraminidase structure for treating drug-resistant H5N1 virus. Biochem Biophys Res Commun. 2007 Oct 19;362(2):525-31. Epub 2007 Aug 13. [PubMed:17707775]
  5. Wang MZ, Tai CY, Mendel DB: Mechanism by which mutations at his274 alter sensitivity of influenza a virus n1 neuraminidase to oseltamivir carboxylate and zanamivir. Antimicrob Agents Chemother. 2002 Dec;46(12):3809-16. [PubMed:12435681]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Exo-alpha-sialidase activity
Specific Function
Catalyzes the removal of sialic acid (N-acetylneuraminic acid) moities from glycoproteins and glycolipids. To be active, it is strictly dependent on its presence in the multienzyme complex. Appears...
Gene Name
NEU1
Uniprot ID
Q99519
Uniprot Name
Sialidase-1
Molecular Weight
45466.96 Da
References
  1. Chavas LM, Kato R, Suzuki N, von Itzstein M, Mann MC, Thomson RJ, Dyason JC, McKimm-Breschkin J, Fusi P, Tringali C, Venerando B, Tettamanti G, Monti E, Wakatsuki S: Complexity in influenza virus targeted drug design: interaction with human sialidases. J Med Chem. 2010 Apr 8;53(7):2998-3002. doi: 10.1021/jm100078r. [PubMed:20222714]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Exo-alpha-(2->8)-sialidase activity
Specific Function
Catalyzes the removal of sialic acid (N-acetylneuraminic acid) moities from glycoproteins, oligosaccharides and gangliosides.
Gene Name
NEU2
Uniprot ID
Q9Y3R4
Uniprot Name
Sialidase-2
Molecular Weight
42253.345 Da
References
  1. Chavas LM, Kato R, Suzuki N, von Itzstein M, Mann MC, Thomson RJ, Dyason JC, McKimm-Breschkin J, Fusi P, Tringali C, Venerando B, Tettamanti G, Monti E, Wakatsuki S: Complexity in influenza virus targeted drug design: interaction with human sialidases. J Med Chem. 2010 Apr 8;53(7):2998-3002. doi: 10.1021/jm100078r. [PubMed:20222714]

Enzymes

Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Substrate
General Function
Triglyceride lipase activity
Specific Function
Involved in the detoxification of xenobiotics and in the activation of ester and amide prodrugs. Hydrolyzes aromatic and aliphatic esters, but has no catalytic activity toward amides or a fatty acy...
Gene Name
CES1
Uniprot ID
P23141
Uniprot Name
Liver carboxylesterase 1
Molecular Weight
62520.62 Da
References
  1. Zhu HJ, Markowitz JS: Activation of the antiviral prodrug oseltamivir is impaired by two newly identified carboxylesterase 1 variants. Drug Metab Dispos. 2009 Feb;37(2):264-7. doi: 10.1124/dmd.108.024943. Epub 2008 Nov 20. [PubMed:19022936]
  2. Shi D, Yang J, Yang D, LeCluyse EL, Black C, You L, Akhlaghi F, Yan B: Anti-influenza prodrug oseltamivir is activated by carboxylesterase human carboxylesterase 1, and the activation is inhibited by antiplatelet agent clopidogrel. J Pharmacol Exp Ther. 2006 Dec;319(3):1477-84. Epub 2006 Sep 11. [PubMed:16966469]
  3. Wattanagoon Y, Stepniewska K, Lindegardh N, Pukrittayakamee S, Silachamroon U, Piyaphanee W, Singtoroj T, Hanpithakpong W, Davies G, Tarning J, Pongtavornpinyo W, Fukuda C, Singhasivanon P, Day NP, White NJ: Pharmacokinetics of high-dose oseltamivir in healthy volunteers. Antimicrob Agents Chemother. 2009 Mar;53(3):945-52. doi: 10.1128/AAC.00588-08. Epub 2008 Dec 22. [PubMed:19104028]

Transporters

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Atpase activity, coupled to transmembrane movement of substances
Specific Function
May be an organic anion pump relevant to cellular detoxification.
Gene Name
ABCC4
Uniprot ID
O15439
Uniprot Name
Multidrug resistance-associated protein 4
Molecular Weight
149525.33 Da
References
  1. Ose A, Ito M, Kusuhara H, Yamatsugu K, Kanai M, Shibasaki M, Hosokawa M, Schuetz JD, Sugiyama Y: Limited brain distribution of [3R,4R,5S]-4-acetamido-5-amino-3-(1-ethylpropoxy)-1-cyclohexene-1-carboxylate phosphate (Ro 64-0802), a pharmacologically active form of oseltamivir, by active efflux across the blood-brain barrier mediated by organic anion transporter 3 (Oat3/Slc22a8) and multidrug resistance-associated protein 4 (Mrp4/Abcc4). Drug Metab Dispos. 2009 Feb;37(2):315-21. doi: 10.1124/dmd.108.024018. Epub 2008 Nov 24. [PubMed:19029202]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Proton-dependent oligopeptide secondary active transmembrane transporter activity
Specific Function
Proton-coupled intake of oligopeptides of 2 to 4 amino acids with a preference for dipeptides. May constitute a major route for the absorption of protein digestion end-products.
Gene Name
SLC15A1
Uniprot ID
P46059
Uniprot Name
Solute carrier family 15 member 1
Molecular Weight
78805.265 Da
References
  1. Ogihara T, Kano T, Wagatsuma T, Wada S, Yabuuchi H, Enomoto S, Morimoto K, Shirasaka Y, Kobayashi S, Tamai I: Oseltamivir (tamiflu) is a substrate of peptide transporter 1. Drug Metab Dispos. 2009 Aug;37(8):1676-81. doi: 10.1124/dmd.109.026922. Epub 2009 May 13. [PubMed:19439487]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Sodium-independent organic anion transmembrane transporter activity
Specific Function
Plays an important role in the excretion/detoxification of endogenous and exogenous organic anions, especially from the brain and kidney. Involved in the transport basolateral of steviol, fexofenad...
Gene Name
SLC22A8
Uniprot ID
Q8TCC7
Uniprot Name
Solute carrier family 22 member 8
Molecular Weight
59855.585 Da
References
  1. Ose A, Ito M, Kusuhara H, Yamatsugu K, Kanai M, Shibasaki M, Hosokawa M, Schuetz JD, Sugiyama Y: Limited brain distribution of [3R,4R,5S]-4-acetamido-5-amino-3-(1-ethylpropoxy)-1-cyclohexene-1-carboxylate phosphate (Ro 64-0802), a pharmacologically active form of oseltamivir, by active efflux across the blood-brain barrier mediated by organic anion transporter 3 (Oat3/Slc22a8) and multidrug resistance-associated protein 4 (Mrp4/Abcc4). Drug Metab Dispos. 2009 Feb;37(2):315-21. doi: 10.1124/dmd.108.024018. Epub 2008 Nov 24. [PubMed:19029202]

Drug created on June 13, 2005 07:24 / Updated on September 17, 2019 03:31